Nedaplatin plus pemetrexed or cisplatin plus pemetrexed as first-line chemotherapy for EGFR/ALK-negative advanced lung adenocarcinoma (NACA): A multicenter, open-label, non-inferiority, randomized, phase III trial.
Authors: Xue Hou, Weineng Feng, Hao Long, Qing Bu, Chengzhi Zhou, Huafeng LIU, Chao CHENG, Lin WANG, Guowu Wu, Shimin Wen, Tong Zhou, Xicheng Wang, Dongying LIU, Xiaoxia Bi, Encun Hou, Hua Jiang, Likun Chen
Journal: Journal of Clinical Oncology (2022)

9089 Background: Platinum-based chemotherapy is the backbone of treatment for advanced non-small cell lung cancer. Cisplatin has well-known side effects such as gastrointestinal reaction and fatigue, and nedaplatin was developed to be an alternative platinum with less toxicity. We aimed to compare nedaplatin plus pemetrexed was non-inferior to cisplatin plus pemetrexed as first-line chemotherapy for advanced EGFR/ALK-negative lung adenocarcinoma. Methods: We did an open-label, randomized, phase III trial at 15 centers in China. Advanced lung adenocarcinoma patients with EGFR/ALK-negative status were randomly assigned to receive nedaplatin 90 mg/m 2 or cisplatin 75 mg/m 2 plus pemetrexed 500 mg/m 2 for 6 cycles as first-line treatment, and pemetrexed maintenance for those without progressive disease. The primary endpoint was progression-free survival (PFS), non-inferiority was shown if the upper limit of the 95% CI for the hazard ratio (HR) of PFS did not exceed 1.30. Secondary endpoints included objective response, overall survival and toxicity. This trial is registered with ClinicalTrials.gov, number NCT02607592. Results: Between Sep 2015 and May 2021, 218 patients were randomized to nedaplatin group (n = 111) or cisplatin group (n = 107). In the intention-to-treat population, median PFS time was 6.87 months (95%CI, 5.25 to 8.49) in the nedaplatin group and 5.53 months (95%CI, 4.57 to 6.50) in the cisplatin group, with a HR of 0.76 (95%CI, 0.56 to 1.03, p= 0.078). In the per-protocol population (nedaplatin group, n = 105; cisplatin group, n = 94), median PFS time was 6.87 months (95%CI, 5.36 to 8.37) and 5.20 months (95%CI, 4.03 to 6.37) respectively, with a HR of 0.76 (95%CI, 0.56 to 1.03, p= 0.082). Overall response rate was 41.9% in nedaplatin group and 26.6% in cisplatin group ( p= 0.026). A significantly higher frequency of any grade nausea and vomiting (51[53.68%] of 95 in the cisplatin group vs 30[28.04%] of 107 in the nedaplatin group, p&lt; 0.001), fatigue (37[38.95%] vs 27[25.23%], p= 0.037), and constipation (15[15.79%] vs 5[4.67%], p= 0.008) were reported in the cisplatin group compared with the nedaplatin group. Higher rate of grade 3/4 nausea and vomiting was observed in cisplatin group (10[10.53%] vs 0, p= 0.001). Patients in the nedaplatin group had higher frequency of thrombocytopenia but without statistical significance (any grade: 28[26.17%] of 107 in the nedaplatin group vs17[17.89%] of 95 in the cisplatin group, p= 0.158; grade 3/4: 8[7.48%] in the nedaplatin group vs 3[3.16%] in the cisplatin group, p= 0.177). Conclusions: Our findings show that nedaplatin plus pemetrexed is not inferior to cisplatin plus pemetrexed in progression-free survival, with less toxicities, which represents an alternative chemotherapy regimen for EGFR/ALK-negative advanced lung adenocarcinoma. Clinical trial information: NCT02607592.